Document Detail

Intact IGF-binding protein-4 and -5 and their respective fragments isolated from chronic renal failure serum differentially modulate IGF-I actions in cultured growth plate chondrocytes.
MedLine Citation:
PMID:  11675416     Owner:  NLM     Status:  MEDLINE    
Impairment of longitudinal growth among children with chronic renal failure (CRF) may be partly attributable to the inhibition of insulin-like growth factor (IGF) activity by an excess amount of high-affinity IGF-binding proteins (IGFBP). Elevated levels of immunoreactive IGFBP-4 in CRF serum are inversely correlated with the standardized heights of these children, whereas levels of IGFBP-5, which circulates mainly as proteolyzed fragments, are positively correlated with growth parameters. To delineate the respective effects of these IGFBP on growth cartilage, the biologic effects of intact and fragmented forms of IGFBP-4 and IGFBP-5 on rat growth plate chondrocytes in primary cultures were characterized. Intact IGFBP-4 and IGFBP-5 and the amino-terminal fragment IGFBP-5(1-169) were recombinant proteins; the carboxy-terminal fragments IGFBP-5(144-252) and IGFBP-4(136-237) and the amino-terminal fragment IGFBP-4(1-122) were purified to homogeneity from CRF hemofiltrates. Intact IGFBP-4 and, to a lesser extent, IGFBP-4(1-122) inhibited IGF-I-induced cell proliferation. In contrast, intact IGFBP-5 was stimulatory in the absence or presence of exogenous IGF-I, whereas the amino-terminal fragment IGFBP-5(1-169) was inhibitory. Studies on the mechanism by which IGFBP-4 and IGFBP-5 exert opposite effects on chondrocyte proliferation demonstrated that intact IGFBP-4 prevented the binding of (125)I-IGF-I to chondrocytes, whereas intact IGFBP-5 enhanced ligand binding and was able to bind specifically to the cell membrane. These data suggest that intact IGFBP-4 and, to a lesser extent, IGFBP-4(1-122) act exclusively as growth-inhibitory binding proteins in the growth cartilage. IGFBP-5, however, can either stimulate (if it remains intact) or inhibit (if amino-terminal forms predominate) IGF-I-stimulated chondrocyte proliferation.
D Kiepe; D L Andress; S Mohan; L Ständker; T Ulinski; R Himmele; O Mehls; B Tönshoff
Related Documents :
6994716 - Binding of insulin to bovine liver plasma membrane. use of insulin analogues modified a...
16886086 - A cationic lanthanide complex binds selectively to phosphorylated tyrosine sites, aidin...
17434446 - N-acetylgalactosaminyltransferase 14, a novel insulin-like growth factor binding protei...
2973786 - Classification of the insulin-like growth factor binding proteins into three distinct c...
2162036 - Localisation and characterisation of functional vasoactive intestinal peptide receptors...
19358706 - Identification of distinct set/taf-ibeta domains required for core histone binding and ...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  12     ISSN:  1046-6673     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-10-24     Completed Date:  2002-02-15     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2400-10     Citation Subset:  IM    
Division of Pediatric Nephrology, University Children's Hospital Heidelberg, Heidelberg, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cell Division / drug effects
Chondrocytes / cytology,  drug effects*,  metabolism
Growth Plate / cytology,  drug effects*,  metabolism
Insulin-Like Growth Factor Binding Protein 4 / isolation & purification*,  metabolism,  pharmacology*
Insulin-Like Growth Factor Binding Protein 5 / isolation & purification*,  metabolism,  pharmacology*
Insulin-Like Growth Factor I / metabolism,  pharmacology*
Kidney Failure, Chronic / blood*
Peptide Fragments / isolation & purification
RNA, Messenger / metabolism
Rats, Sprague-Dawley
Receptor, IGF Type 1 / genetics
Grant Support
Reg. No./Substance:
0/Insulin-Like Growth Factor Binding Protein 4; 0/Insulin-Like Growth Factor Binding Protein 5; 0/Peptide Fragments; 0/RNA, Messenger; 67763-96-6/Insulin-Like Growth Factor I; EC, IGF Type 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Loss of tubular bone morphogenetic protein-7 in diabetic nephropathy.
Next Document:  Survival and development of cardiovascular disease by modality of treatment in patients with end-sta...